Acute decompensation (AD) of cirrhosis is defined by the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination of these, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF), while their absence defines AD. We designed the PREDICT study, a European, prospective, observational study, to characterize the clinical course of AD and predict ACLF. A total of 1071 patients with AD were enrolled to collect detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed-up for 3 months. The 12-month outcomes (liver transplantation, and death) were also recorded. Three groups of patients were identified: Pre-ACLF patients (n=218), who developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but not developing ACLF and had 21.0% and 35.6% mortality rates. Stable decompensated cirrhosis (SDC) patients (n = 620) who were neither readmitted, nor developed ACLF and showed a 1-year mortality of only 9.5%. The 3 groups differed significantly in the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in the SDC) and prevalence of surrogates of severe portal hypertension throughout the study (high in UDC versus low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with three different clinical courses and two major pathophysiological mechanisms: systemic inflammation and portal hypertension. Prediction of ACLF development remains a major future task.

Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90-day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes.

Background: The pandemic of coronavirus disease 2019 (COVID‐19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID‐19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non‐critically ill patients with COVID‐19.Methods: In this multicentre, retrospective study, we collected data about 565 inpatients with COVID‐19. Data on LFTs were collected at admission and every 7 ± 2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU).Results: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20% vs 8%; P < .001), acute kidney injury (22% vs 13%, P = .009), need for mechanical ventilation (14% vs 6%; P = .005) and mortality (21% vs 11%; P = .004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR = 3.53; P < .001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint.Conclusions: LFTs abnormality is common at admission in patients with COVID‐19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.